Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma

Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma.

The clinical relevance of gene expression based prognostic signatures in colorectal cancer.

Biomarkers are vital in healthcare as they provide valuable insights into disease diagnosis, prognosis, treatment response, and personalized medicine. They serve as objective indicators, enabling early detection and intervention, leading to improved patient outcomes and reduced costs. Biomarkers also guide treatment decisions by predicting disease outcomes and facilitating individualized treatment plans. They play a role in monitoring disease progression, adjusting treatments, and detecting early signs of recurrence. Furthermore, biomarkers enhance drug development and clinical trials by identifying suitable patients and accelerating the approval process. In this review paper, we described a variety of biomarkers applicable for cancer detection and diagnosis, such as imaging-based diagnosis (CT, SPECT, MRI, and PET), blood-based biomarkers (proteins, genes, mRNA, and peptides), cell imaging-based diagnosis (needle biopsy and CTC), tissue imaging-based diagnosis (IHC), and genetic-based biomarkers (RNAseq, scRNAseq, and spatial transcriptomics).

Biomarkers in Cancer Detection, Diagnosis, and Prognosis

microRNAs (miRNAs) are a class of small non-coding RNAs that regulate the expression of their target mRNAs post transcriptionally. miRNAs are known to regulate not just a gene but the whole gene network (signaling pathways). Accumulating evidence(s) suggests that miRNAs can work either as oncogenes or tumor suppressors, but some miRNAs have a dual nature since they can act as both. miRNA 205 (miR-205) is one such highly conserved miRNA that can act as both, oncomiRNA and tumor suppressor. However, most reports confirm its emerging role as a tumor suppressor in many cancers. This review focuses on the downregulated expression of miR-205 and discusses its dysregulation in breast, prostate, skin, liver, gliomas, pancreatic, colorectal and renal cancers. This review also confers its role in tumor initiation, progression, cell proliferation, epithelial to mesenchymal transition, and tumor metastasis. Restoration of miR-205 makes cells more sensitive to drug treatments and mitigates drug resistance. Additionally, the importance of miR-205 in chemosensitization and its utilization as potential biomedicine and nanotherapy is described. Together, this review research article sheds a light on its application as a diagnostic and therapeutic marker, and as a biomedicine in cancer.

/pdf/mir-205-a-potential-biomedicine-for-cancer-therapy-4jixrw4bbs.pdf

miR-205: A Potential Biomedicine for Cancer Therapy

Long non-coding RNAs (lncRNAs) play key roles in tumorigenesis. It has been reported that the lncRNA nuclear-enriched abundant transcript 1 (NEAT1) may act as an oncogenic regulator in several cancers. However, the biological mechanism of action of NEAT1, particularly the miRNA sponge role in colorectal cancer (CRC), has not been fully elucidated. In our study, the expression of NEAT1, miR-205-5p, and vascular endothelial growth factor A (VEGFA) in CRC cell lines were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. Cell migration and invasion were examined by wound healing and transwell assays, respectively. RNA-binding protein immunoprecipitation (RIP), and dual-luciferase and RNA pull-down assays were conducted to determine the correlation between miR-205-5p and NEAT1 or VEGFA. VEGFA, matrix metalloproteinase (MMP)2, and MMP9 protein and mRNA expression were measured by western blotting and RT-qPCR analysis, respectively. Our results demonstrated high expression of NEAT1 and VEGFA and low expression of miR-205-5p in CRC cell lines. The RIP and dual-luciferase assays confirmed miR-205-5p as a target of NEAT1. In addition, VEGFA was identified as a direct target of miR-205-5p. Inhibition of NEAT1 or overexpression of miR-205-5p was able to repress VEGFA expression. Moreover, downregulation of NEAT1 and VEGFA inhibited cell proliferation, migration, and invasion. NEAT1 overexpression facilitated tumor growth by modulating miR-205-5p. Taken together, lncRNA NEAT1 was found to be upregulated in CRC cell lines, promoting CRC cell proliferation, migration, and invasion through regulating the miR-205-5p/VEGFA signaling pathway. These findings suggest that NEAT1 may be a promising biomarker in CRC diagnosis and treatment.

Long non-coding RNA NEAT1 promotes colorectal cancer progression by regulating miR-205-5p/VEGFA axis

Objective: Our study aimed to construct a robust long non-coding RNA (lncRNA) prognostic signature for colorectal cancer (CRC) metastasis. Methods: Differentially expressed lncRNAs were identified between metastatic CRC and non-metastatic CRC samples from The Cancer Genome Atlas Database (TCGA) using the edgeR package. The differentially expressed lncRNAs with prognosis of patients with CRC metastasis were identified by univariate Cox regression analysis, followed by a stepwise multivariate Cox regression model. The survminer package in R was used to identify the optimal cutoff point for high-risk and low-risk groups. The receiver operating characteristic (ROC) curves were plotted to assess this signature. To explore potential signaling pathways associated with these lncRNAs, Gene Set Enrichment Analysis (GSEA) was performed. Results: A 6-lncRNA signature was built based on the lncRNA expression profile for CRC metastasis. The optimal cutoff value was used to classify high-risk and low-risk groups using the survminer package. The high-risk groups could have poorer survival time than the low-risk groups. ROC curve result indicated that this lncRNA signature had high sensitivity and accuracy. GSEA analysis results showed that the six lncRNAs were significantly enriched in several CRC metastasis-related signaling pathways such as "cell cycle," "DNA replication," "mismatch repair," "oxidative phosphorylation," "regulation of autophagy," and "insulin signaling pathway." Conclusion: Our study constructed a 6-lncRNA model for predicting the survival outcomes of patients with CRC metastasis, which could become potential prognostic biomarkers, and therapeutic targets for CRC metastasis.

/pdf/a-robust-6-lncrna-prognostic-signature-for-predicting-the-3z0koe69sz.pdf

A Robust 6-lncRNA Prognostic Signature for Predicting the Prognosis of Patients With Colorectal Cancer Metastasis.

MicroRNAs (miRNAs) are small non-coding RNAs, which are critical in a diverse range of biological processes, including development, differentiation, homeostasis, and in the formation of diseases by accelerating and/or inhibiting the translation of mRNAs. The present study aimed to examine the potential role of miRNA (miR)-205-5p in the developmental process of colorectal cancer (CRC) through protein-tyrosine kinase 7 (PTK7). Initially, TargetScan was used to predict the miRNA target sites in the sequence of the PTK7 3′-untranslated region. It was then found that the mRNA expression level of miR-205-5p was lower in CRC cells, determined using reverse transcription-quantitative polymerase chain reaction analysis, and there was a negative correlation between miR-205-5p and PTK7 in CRC tissues. It was also found that miR-205-5p regulated the gene transcription of PTK7, determined using a luciferase reporter assay. The results of RT-qPCR and western blot analyses in human colorectal cancer revealed that miR-205-5p suppressed the expression of PTK7. Finally, it was revealed that miR-205-5p restricted the proliferation ability of CRC cells through inhibiting PTK7, which was determined using colony forming and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. miR-205-5p accelerated cell apoptosis through inhibiting PTK7, demonstrated using Annexin V-FITC/propidium iodide staining. The results of a Transwell assay indicated that miR-205-5p inhibited the migration and invasion abilities of CRC cells through inhibiting PTK7. Therefore, miR-205-5p is involved in the proliferation, migration and invasion of CRC through inhibiting PTK7.

/pdf/mir-205-5p-ptk7-axis-is-involved-in-the-proliferation-clz7bfv69j.pdf

miR‑205‑5p/PTK7 axis is involved in the proliferation, migration and invasion of colorectal cancer cells.

Long noncoding RNAs (lncRNAs) are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, most of the lncRNAs are still being undiscovered, and conclusive experimental evidence for their functional relevance continues to be lacking for most malignancies. We have found that lncRNA long intergenic non-protein-coding RNA 341 (LINC00341) is aberrantly downregulated by microarray-based screenings on nonmetastatic and metastatic colorectal carcinoma (CRC) specimens; LINC00341 is a novel long intergenic non-protein-coding RNA with unknown functions. LINC00341 overexpression restricts tumour growth and promotes its apoptosis. Instead, LINC00341 silencing accelerates CRC cell proliferation and migration. RNA-pulldown assay identifies LINC00341 physically binds to HMGB2 and stabilizes the localization of HMGB2 in the cytoplasm. Notably, LINC00341 knockdown leads to the shift of HMGB2 into nuclear, in which it triggers epithelial to mesenchymal transition (EMT) programming. Moreover, LINC00341 can also promote apoptosis. SIGNIFICANCE OF THE STUDY: LncRNAs are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, the function of lncRNA still needs further exploration. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects colorectal carcinoma by preventing migration and apoptosis. The results will help further explore the molecular details about the progression of colorectal carcinoma and stimulate efforts to develop effective therapies.

The long noncoding RNA LINC00341 suppresses colorectal carcinoma by preventing cell migration and apoptosis.

Colorectal cancer (CRC) is the third most common cancer worldwide. This study aimed to explore the regulatory mechanisms of miRNAs in CRC. Differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) in CRC tissue samples compared with control samples in mRNA and miRNA datasets were screened. Functional and pathway enrichment analysis of the DEGs was carried out. Targets of the DEMs were identified. Overlaps between the DEGs and targets of DEMs were selected. The miRNA-mRNA regulatory network of these overlaps was constructed and visualized. The candidate genes selected were validated by quantitative real-time PCR. DEGs were identified and considered DEGs-1 and DEGs-2. A total of 584 genes in DEGs-1 and 527 genes in DEGs-2 were obtained, including 465 overlaps, and 44 DEMs were identified. The overlaps were enriched in 46 Gene Ontology terms and 19 Kyoto Encyclopedia of Genes and Genomes pathways. Moreover, 137 overlapped genes between targets of the DEMs and the 465 overlaps were obtained. The miRNA-mRNA regulating network of the 137 overlapped genes was constructed. Extracellular matrix-related proteins and pathways might play critical roles in the development of CRC. The quantitative real-time PCR results of the candidates were in agreement with the bioinformatics analysis. miR-128, miR-182, and miR-143 might be key miRNAs regulating cell proliferation and metastasis of CRC.

Construction of an miRNA-mRNA regulatory network in colorectal cancer with bioinformatics methods.

Long noncoding RNAs (lncRNAs) have recently emerged as important biomarkers of cancer progression. Here, we proposed to develop a lncRNA-based signature with a prognostic value for colorectal cancer (CRC) overall survival (OS). Through mining microarray datasets, we analyzed the lncRNA expression profiles of 122 patients with CRC from Gene Expression Omnibus. Associations between lncRNA and CRC OS were firstly evaluated through univariate Cox regression analysis. A random survival forest method was applied for further screening of the lncRNA signature, which resulted in eight lncRNAs, including PEG3-AS1, LOC100505715, MINCR, DBH-AS1, LINC00664, FAM224A, LOC642852, and LINC00662. Combination of the eight lncRNAs weighted by their multivariate Cox regression coefficients formed a prognostic signature, through which, we could divide the 122 patients with CRC into two subgroups with significantly different OS. Good robustness of the lncRNA signature's prognostic value was verified through an independent data set consisting of 55 patients with CRC. In addition, gene set enrichment analysis indicated the potential association between high prognostic value and oxygen metabolism-related processes. This result should indicate that lncRNAs could be a useful signature for CRC prognosis.

An eight-long noncoding RNA expression signature for colorectal cancer patients' prognosis

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